Delving into the Latest Updates on ANG-453 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Tubulin

Mechanism

Tubulin inhibitors

Therapeutic Areas

NeoplasmsDigestive System DisordersUrogenital Diseases

Active Indication-

Inactive Indication

Metastatic Colorectal CarcinomaMetastatic Renal Cell CarcinomaNeoplasm Metastasis+ [1]

Originator Organization

Angiogene Pharmaceuticals Ltd.

Active Organization-

Inactive Organization

AstraZeneca PLCAngiogene Pharmaceuticals Ltd.

Drug Highest PhaseSuspendedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC20H24NO8P

InChIKeyUGBMEXLBFDAOGL-INIZCTEOSA-N

CAS Registry219923-05-4

The application of in vivo magnetic resonance (MR) in drug development has several requirements that differ significantly from most applications primarily because the biopharmaceutical industry must develop new safe and effective drugs more quickly and at lower cost in a highly regulated environment. In vivo MR is recognized as a useful method to provide biomarkers for target engagement, treatment response, safety and mechanism of action that can be translated between animal and clinical studies. Thus, it has the potential to help identify drugs that are more likely to be safe and effective earlier in the process of drug development, which may help reduce the time and money required to get new drugs to patients with an unmet medical need. A brief introduction of how novel drugs are discovered and developed, what drives the biopharmaceutical industry's interest in using biomarkers and what it takes to use MR as a biomarker to support drug development, including regulatory concerns, provides context for understanding what makes the application of in vivo MR in drug development different from most others. Exploration of three programs (trebananib, ZD6126 and axitinib) using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in the development of antivascular agents provides insight into how in vivo MR biomarkers impact drug discovery and development and the limitations of biomarkers.

01 Sep 2015·Microvascular ResearchQ3 · MEDICINE

Detecting microvascular changes in the mouse spleen using optical computed tomography

Q3 · MEDICINE

Article

Author: David J. Collins ; Simon J. Doran ; Jessica K.R. Boult ; Ciara M. McErlean ; Martin O. Leach ; Simon P. Robinson

Methods of monitoring drug toxicity in off-target organs are very important in the development of effective and safe drugs. Standard 2-D techniques, such as histology, are prone to sampling errors and can miss important information. We demonstrate a novel application of optical computed tomography (CT) imaging to quantitatively assess, in 3-D, the response of adult murine spleen to off-target drug toxicity induced by treatment with the vascular disrupting agent ZD6126. Reconstructed images from optical CT scans sensitive to haemoglobin absorption reveal detailed, high-contrast 3-D maps of splenic structure and microvasculature. A significant difference in total splenic volume was found between vehicle and ZD6126-treated cohorts, with mean volumes of 61±3mm(3) and 44±3mm(3) respectively (both n=3, p=0.05). Textural statistics for each sample were calculated using grey-level co-occurrence matrices (GLCMs). Standard 2-D GLCM analysis was found to be slice-dependent while 3-D GLCM contrast and homogeneity analysis resulted in separation of the vehicle and ZD6126-treated cohorts over a range of length scales.

17 Mar 2015·Current Medicinal ChemistryQ2 · MEDICINE

Tubulin Colchicine Binding Site Inhibitors as Vascular Disrupting Agents in Clinical Developments

Q2 · MEDICINE

Review

Author: Liu, Zhao-Peng ; Liu, Yan-Na ; Ji, Ya-Ting

Tumor vasculature is an important target in cancer treatment. Two distinct vasculartargeting therapeutic strategies are applied to attack cancer cells indirectly. The antiangiogenic approach intervenes in the neovascularization processes and blocks the formation of new blood vessels, while th e antivascular approach targets the established tumor blood vessels, making vascular shutdown and resulting in rapid haemorrhagic necrosis and tumor cell death. A number of compounds with diverse structural scaffolds have been designed to target tumor vasculature and they are called vascular disrupting agents (VDAs). The biological or ligand-directed VDAs utilize antibodies, peptides or growth factors to deliver toxins or pro-coagulants or proapoptotic affectors to tumor-related blood vessels, while the small-molecule VDAs selectively target tumor blood vessels and have little effects on the normal endothelium. Among the small-molecule VDAs, the tubulin colchicine binding site inhibitors have been extensively studied and many of them have entered the clinical trials, including CA-4P, CA-1P, AVE8062, OXi4503, CKD-516, BNC105P, ABT-751, CYT- 997, ZD6126, NPI-2358, MN-029 and EPC2407. This review makes a summary of the small-molecule VDAs in clinical developments and highlights some potential VDA leads or candidates for the treatment of tumors.

100 Deals associated with ANG-453

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11872

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 2	GB	Angiogene Pharmaceuticals Ltd.	07 Mar 2006
Metastatic Colorectal Carcinoma	Phase 2	US	AstraZeneca PLC	01 Sep 2003
Neoplasm Metastasis	Phase 2	US	AstraZeneca PLC	01 Sep 2003
Metastatic Renal Cell Carcinoma	Phase 2	US	AstraZeneca PLC	01 Aug 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ZD6126 (ASTRO2002)	Not Applicable	Neoplasms	-	ZD6126	fzyrkoeroz(kdlsyhysrz) = abturhhakx ejbyjjsarc (dwljijqxca, 0.4) View more	Positive	01 Oct 2002
				ZD6126 (Control)	fzyrkoeroz(kdlsyhysrz) = xpmycxqszb ejbyjjsarc (dwljijqxca, 0.2) View more